[Retracted] Silencing cyclin­dependent kinase inhibitor 3 inhibits the migration of breast cancer cell lines.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the GAPDH control western blotting data shown in Fig. 1C were strikingly similar to data appearing in different form in another article written by different authors at different research institutes [Chen Y, Guo Y, Yang H, Shi G, Xu G, Shi J, Yin N and Chen D: TRIM66 overexpression contributes to osteosarcoma carcinogenesis and indicates poor survival outcome. Oncotarget 6: 23708­23719, 2015]. Moreover, a pair of data panels showing the results from cell­cycle experiments purportedly performed under different experimental conditions in Fig. 4A appeared to be strikingly similar. Owing to the fact that the contentious data in the above article were already under consideration for publication prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 14: 1523­1530, 2016; DOI: 10.3892/mmr.2016.5401].

Inorganic pyrophosphatase 1 activates the phosphatidylinositol 3-kinase/Akt signaling to promote tumorigenicity and stemness properties in colorectal cancer.

Colorectal cancer (CRC) is a common malignant tumor of the human digestive tract. Inorganic pyrophosphatase 1 (PPA1) plays an imperative role in the advancement of malignant tumors, but its function in CRC is ill-defined. In this study, we inspected the functions of PPA1 in CRC. The abundance of PPA1 in CRC tissues was analyzed by utilizing publicly available data from the The Cancer Genome Atlas and Human Protein Atlas project. Cell counting kit-8 assay and 5-ethynyl-2'-deoxyuridine assay were used to evaluate the viability and proliferation of CRC cells. Bioinformatics analysis was used to forecast the PPA1 related genes and signal pathways in CRC. The protein expression was examined by western blot. The xenograft model was implemented to determine the influence of PPA1 in CRC in vivo. Proliferating cell nuclear antigen, CD133, and CD44 contents in xenograft tumors were evaluated by immunohistochemistry. In the present study, we found that the PPA1 content was heightened in CRC, and the diagnostic value of PPA1 in CRC was enormous. Overexpression of PPA1 enhanced cell proliferation and stemness properties in CRC cells, while downregulation of PPA1 had the opposite effects. PPA1 promoted the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Activation of the PI3K/Akt signaling reversed the effect of PPA1 silencing on cell proliferation and stemness properties in CRC cells. Silencing of PPA1 reduced xenograft tumor growth via modulating the PI3K/Akt signaling pathway in vivo. In conclusion, PPA1 promoted cell proliferation and stemness properties in CRC by activating the PI3K/Akt signaling pathway.

Metabolic Syndrome and Its Components are Associated with In-Hospital Complications after Thoracic Endovascular Aortic Repair for Acute Type B Aortic Dissection.

BACKGROUND: This study aimed to explore whether and to what extent metabolic syndrome (MetS) and its components are associated with in-hospital complications in patients with acute type B aortic dissection after thoracic endovascular aortic repair (TEVAR). METHODS: We retrospectively enrolled 684 patients who had undergone TEVAR. Demographic and clinical data were collected and subgroup analysis, mixed-model regression analysis, scoring systems, and receiver operating characteristic (ROC) curve analyses were performed. RESULTS: Overall, 684 inpatients were assigned to the poor outcome (n = 90) or no complications (n = 594) group. Compared to the no complications group, the poor outcome group had a higher incidence of MetS (44 [48.9%] vs. 120 [20.2%], P < 0.05). In the subgroup analysis, in-hospital complications were present in 3.1%, 6.6%, 11.9%, 20.7%, 40.0%, and 62.5% of patients in the 6 groups who met the 0, 1, 2, 3, 4, and 5 MetS diagnostic criteria, respectively. On multivariable logistic regression, hypertension (odds ratio [OR]: 2.680; 95% confidence interval [CI]: 1.571-4.570), type 2 diabetes (OR: 2.135; 95% CI: 1.192-3.824), quartiles of body mass index (OR: 1.801; 95% CI: 1.415-2.291), high-density lipoprotein cholesterol (OR: 0.763; 95% CI: 0.611-0.953), and systolic blood pressure (OR: 1.894; 95% CI: 1.486-2.413) were independent factors for in-hospital complications after adjustment for other risk factors. After adjusting for potential confounding factors, MetS was an independent risk factor for in-hospital complications. We established a scoring system for each component and the area under the ROC curve was 0.664 (95% CI: 0.618-0.710) in all patients, 0.672 (95% CI: 0.595-0.749) in patients with MetS, and 0.610 (95% CI: 0.552-0.667) in patients without MetS, as determined by ROC analysis. CONCLUSIONS: MetS, especially the blood pressure component, confers a greater risk of in-hospital complications in patients with acute type B aortic dissection after TEVAR.

Circular RNA circ-CD44 regulates chemotherapy resistance by targeting the miR-330-5p/ABCC1 axis in colorectal cancer cells.

BACKGROUND: Colorectal cancer (CRC) is a common malignant tumor worldwide, ranking fourth for incidence. Recently, circular RNAs (circRNAs) have been demonstrated to play a key role in chemotherapy resistance to CRC treatment. Therefore, the role of circ-CD44 is investigated in CRC. METHODS: The expression levels of circ-CD44, miR-330-5p, and ATP binding cassette subfamily C member 1 (ABCC1) were quantified by real-time quantitative polymerase chain reaction (RT-qPCR) assay. The sensitivity of CRC cells to oxaliplatin (OXA) was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT) assay. Colony-forming experiment was performed to measure the colony-forming ability of CRC cells. The apoptosis, migration, and invasion of CRC cells were determined by flow cytometry and transwell assays. A xenograft experiment was established to clarify the functional role of circ-CD44 silencing in vivo. The interactional relationship among circ-CD44, miR-330-5p, and ABCC1 was confirmed by dual-luciferase reporter and RNA immunoprecipitation assays. The protein expression of ABCC1 was quantified by western blot assay. RESULTS: Circ-CD44 was obviously upregulated in OXA-resistant colorectal cancer tissues and cells. Loss-of-function experiments revealed that inhibition of circ-CD44 suppressed proliferation, migration, and invasion while it increased OXA sensitivity and apoptosis in OXA-resistant colorectal cancer cells, which was overturned by suppression of miR-330-5p; besides, silencing of circ-CD44 also slowed the tumor growth in vivo. Additionally, overexpression of miR-330-5p inhibited chemotherapy resistance, proliferation, migration, and invasion while it induced apoptosis by targeting ABCC1. CONCLUSION: Mechanistically, circ-CD44 functioned as a miRNA sponge for miR-330-5p to upregulate the expression of ABCC1 and regulate chemotherapy resistance in CRC cells.

Midterm Outcomes of Endovascular Therapy for TASC II D Femoropopliteal Lesions with Critical Limb Ischemia: A Retrospective Analysis.

BACKGROUND: This study evaluated the midterm results of endovascular therapy (EVT) for Trans-Atlantic Inter-Society (TASC) II D femoropopliteal lesions in patients with critical limb ischemia (CLI). METHODS: Fifty seven limbs of 54 patients with CLI due to TASC II D femoropopliteal lesions who underwent EVT at the First Hospital of Hebei Medical University were retrospectively analysed in a single-centre, observational study. The patient characteristics, endovascular procedural details, freedom from target lesion revascularization (TLR), patency rates, ulcer healing rate, and limb salvage rate were accessed. RESULTS: The patients' mean age was 68.2 ± 8.2 years. All patients were treated by EVT. The final technical success rate was 98.2% (56/57). There were 23 cases of pain at rest, 18 cases of ulcer, and 15 cases of gangrene. The median length of the treated segment was 286 ± 42 mm (56/56) and the mean number of stents placed per patient was 2.0 ± 0.8 (49/56). The postoperative ankle-brachial index was significantly higher than that of the preoperative ankle-brachial index (P < 0.05). The perioperative complication rate was 10.7% (6/56). The restenosis or occlusion rate was 44.6% (25/56). The estimated rates of freedom from TLR at 1 year, 2 years, and 3 years were 86.8%, 67.0%, and 62.5%, respectively. A univariate analysis showed that predictors of freedom from TLR were the number of runoff vessels, length of the lesion, and complexity of the lesion, while predictors for restenosis or occlusion were the length and the complexity of the lesion. The ulcer healing rate was 93.8%. The limb salvage rates were 76.4%, 74.4%, and 70.9% at 1, 2, and 3 years after treatment, respectively. CONCLUSIONS: The midterm outcomes of EVT for TASC II D femoropopliteal lesions in patients with CLI indicated that this treatment approach is safe and effective and is clinically applicable.

Untargeted metabolomics analysis reveals Mycobacterium tuberculosis strain H37Rv specifically induces tryptophan metabolism in human macrophages.

BACKGROUND: Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tb) remains a global health issue. The characterized virulent M. tb H37Rv, avirulent M. tb H37Ra and BCG strains are widely used as reference strains to investigate the mechanism of TB pathogenicity. Here, we attempted to determine metabolomic signatures associated with the Mycobacterial virulence in human macrophages through comparison of metabolite profile in THP-1-derived macrophages following exposure to the M. tb H37Rv, M. tb H37Ra and BCG strains. RESULTS: Our findings revealed remarkably changed metabolites in infected macrophages compared to uninfected macrophages. H37Rv infection specifically induced 247 differentially changed metabolites compared to H37Ra or BCG infection. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed H37Rv specifically induces tryptophan metabolism. Moreover, quantitative PCR (qPCR) results showed that indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase 2 (TDO2) which converts the tryptophan to a series of biologically second metabolites were up-regulated in H37Rv-infected macrophages compared to H37Ra- or BCG-infected macrophages, confirming the result of enhanced tryptophan metabolism induced by H37Rv infection. These findings indicated that targeting tryptophan (Trp) metabolism may be a potential therapeutic strategy for pulmonary TB. CONCLUSIONS: We identified a number of differentially changed metabolites that specifically induced in H37Rv infected macrophages. These signatures may be associated with the Mycobacterial virulence in human macrophages. The present findings provide a better understanding of the host response associated with the virulence of the Mtb strain.

Effects of Let-7c on the processing of hepatitis B virus associated liver diseases.

BACKGROUND: The most common type of cancer of the digestive system is hepatocellular carcinoma. In China, many patients harbour HBV. The lin28B/Let-7c/MYC axis is associated with the occurrence of many cancers. Therefore, we aimed to illuminate the function of the lin28B/Let-7c/MYC axis in hepatocellular carcinoma. We aimed to evaluate the critical involvement of lin28B and Let-7c in the carcinogenesis of human hepatocellular carcinoma (B-HCC). METHODS: Data from the GEO database were used to analyse differentially expressed genes and IRGs. A protein - protein interaction (PPI) network and Venn diagram were generated to analyse relationships. Real-time RT-PCR, Western blotting, and cell counting kit-8 assays were used to examine the association of lin28B, Let-7c, and MYC with cell proliferation. RESULTS: A total of 2552 functionally annotated differentially expressed RNAs were analysed in HBV patients from the GSE135860 database. In addition, 46 let-7c target genes were screened in HBV patients, and the interactions were analysed through PPI network analysis. The results confirmed that Let-7c and its target genes play a key role in HBV-related diseases. Next, we discovered a gradual decrease in Let-7c expression during the progression from HBV-associated chronic hepatitis (B-CH) and HBV-associated liver cirrhosis (B-LC) to B-HCC. We found evidence for a negative association between lin28B expression and Let-7c expression. The expression of MYC was obviously upregulated when Let-7c was inhibited. CONCLUSION: Our results highlight that Let-7c and lin28B participate in the carcinogenesis of HBV-associated diseases through the lin28B/Let-7c/MYC axis.

Metabolic syndrome and its components are associated with hypoxemia after surgery for acute type A aortic dissection: an observational study.

BACKGROUND: The aim of this study was to explore whether or to what extent metabolic syndrome (METs) and its components were associated with hypoxemia in acute type A aortic dissection (ATAAD) patients after surgery. METHODS: This study involved 271 inpatients who underwent surgery. Demographic and clinical data were collected. Subgroup analysis, mixed model regression analysis, and receiver operating characteristic (ROC) curve analysis were performed, and a scoring system was evaluated. RESULTS: The 271 inpatients were assigned to the hypoxemia group (n = 48) or no hypoxemia group (n = 223) regardless of METs status. Compared to the no hypoxemia group, the hypoxemia group had a higher incidence of METs. Hypoxemia was present in 0%, 3.7%, 19.8%, 51.5%, 90.0% and 100% in the groups of individuals who met the diagnostic criteria of MetS 0, 1, 2, 3, 4 and 5 times, respectively. In the multivariable logistic regression analysis, BMI quartile was still a risk factor for hypoxemia after adjustment for other risk factors. After adjustment for potential confounding factors, METs was an independent risk factor for hypoxemia in several models. After assigning a score for each METs component present, the AUCs were 0.852 (95% CI 0.789-0.914) in all patients, 0.728 (95% CI 0.573-0.882) in patients with METs and 0.744 (95% CI 0.636-0.853) in patients without METs according to receiver operating characteristic analysis. CONCLUSIONS: METs, especially body mass index, confers a greater risk of hypoxemia in ATAAD after surgery.

Crocin ameliorates atherosclerosis by promoting the reverse cholesterol transport and inhibiting the foam cell formation via regulating PPARγ/LXR-α.

Crocin (CRO) is feasible in alleviating atherosclerosis (AS), the mechanism of which was therefore explored in the study. High-fat diet (HFD)-induced apolipoprotein E-deficient (ApoE-/-) mice and lysophosphatidic acid (LPA)-treated macrophages received CRO treatment. Treated macrophage viability was determined via MTT assay. In both murine and macrophage, the lipid level and total Cholesterol/Cholesteryl l Ester (TC/CE) levels were quantified by oil-red-O staining and ELISA, respectively. Lipid droplet, aortic plaque formation and collagen deposition were detected via Oil-red-O staining, hematoxylin-eosin staining and Masson staining, respectively. Liver X Receptor-α (LXR-α), Peroxisome Proliferator-Activated Receptor γ (PPARγ), CD68, PCSK9, CD36, ATP Binding Cassette Subfamily A Member 1 (ABCA1), phosphorylated (p)-AKT, and AKT expressions were detected via Western blot, the former three also being detected using Immunohistochemistry and the first being measured by qRT-PCR. CRO decreased HFD-induced weight gain, ameliorated the abnormal serum lipid levels of HFD-treated mice, and inhibited aortic plaque formation and lipid deposition, and increased collagen fibers, with upregulated high-density lipoprotein-cholesterol (HDL-C) and downregulated TC and low-density lipoprotein-cholesterol (LDL-C). CRO alleviated the HFD-induced upregulations of CD68, PCSK9 and CD36 as well as downregulations of PPARγ/LXR-α, ABCA1 and AKT phosphorylation. In LPA-treated macrophages, CRO alone exerted no effect on the viability yet inhibited the lipid droplets formation and downregulated TC/CE levels. Silent LXR-α reversed the effect of CRO on the lipid droplets formation and levels of lipid metabolism-related factors. CRO ameliorated AS by inhibiting foam cells formation and promoting reverse cholesterol transport via PPARγ/LXR-α.

Enhanced Broad-band Radio Frequency Detection in Nanoscale Magnetic Tunnel Junction by Interface Engineering.

Broad-band radio frequency (RF) detection is of great interest for its potential applications in wireless charging and energy harvesting. Here, we demonstrate that the bandwidth of broad-band RF detection in spin-torque diodes based on magnetic tunnel junctions (MTJs) can be enhanced through engineering the interface perpendicular magnetic anisotropy (PMA) between the CoFeB free layer and the MgO tunnel barrier. An ultrawide RF detection bandwidth of over 3 GHz is observed in the MTJs, and the broad-band RF detection behavior can be modulated by tuning the free layer PMA. Furthermore, a wide RF detection bandwidth (about 1.8 GHz) can be realized even without any external bias field for free layers with a thickness of about 1.65 nm. Finally, the dependence of the broad-band RF detection bandwidth on external magnetic field and RF power is discussed. Our results pave the way for RF energy harvesting for future portable nanoelectronics.

Short- and long-term outcomes in elderly patients with locally advanced non-small-cell lung cancer treated using video-assisted thoracic surgery lobectomy.

BACKGROUND: In recent years, video-assisted thoracic surgery (VATS) lobectomy has been used to treat locally advanced non-small-cell lung cancer (LA-NSCLC). However, VATS has not been reported in elderly patients (≥70 years) with LA-NSCLC. The purpose of this study was to compare short- and long-term outcomes of patients with LA-NSCLC aged ≥70 years and 55-69 years treated with VATS. PATIENTS AND METHODS: From January 2012 to January 2018, a total of 83 patients with LA-NSCLC who were ≥55 years of age underwent VATS. Patients were divided into ≥70 years group (37 cases) and 55-69 years group (46 cases), based on their age at the time of VATS. Short- and long-term outcomes of these two groups of patients were compared. RESULTS: American Society of Anesthesiologists scores of ≥70 years patients were higher than those of 55-69 years patients. No significant differences were observed when comparing the general preoperative data. For short-term outcomes, there was no significant difference between the two groups of patients in length of surgery, intraoperative blood loss, conversion to thoracotomy, postoperative 30-day complication rate and severity, postoperative 30-day mortality, pathological results, compliance with adjuvant chemotherapy, or other factors. Long-term follow-up results showed that recurrence, overall survival, and disease-free survival were similar in both groups. Furthermore, multivariate analysis showed that age was not an independent predictor of overall and disease-free survival. CONCLUSIONS: VATS in elderly patients (≥70 years) with LA-NSCLC can result in short- and long-term outcomes similar to those of 55-69 years patients with LA-NSCLC.

Inhibitory effect of 11-carbonyl-beta-boswellic acid on non-small cell lung cancer H446 cells.

BACKGROUND: The anti-lung tumor potential of 11-carbonyl-ß-boswellic acid was investigated. MATERIALS & METHODS: The inhibitory effects of 11-carbonyl-ß-boswellic acid on non-small cell lung cancer (NSCLC) was assessed by proliferation, apoptosis, cell cycle and molecular mechanisms in NSCLC H446 cells in vitro. The results showed that the growth of H446 cells was significantly inhibited by 11-carbonyl-ß-boswellic acid in a dose- and time-dependent manner. Meanwhile, 11-carbonyl-ß-boswellic acid induced cell apoptosis and cell cycle G2-M phase arrest in H446 cells. RESULTS: Mechanistically, 11-carbonyl-ß-boswellic acid could activate JNK signaling pathway, down-regulate the expression of surviving protein, and activate the cleavage of PARP, leading to marked inhibitory effect on H446 cells. CONCLUSIONS: These findings suggest that 11-carbonyl-ß-boswellic acid may be a potential usefulness for preventing and treatment of NSCLC.

Meta-analysis of the clinical value of abnormally expressed long non-coding RNAs for pancreatic cancer.

Pancreatic cancer (PC) is one of the most lethal malignant neoplasms of the digestive system. Long non-coding RNAs (lncRNAs) are a novel type of non-protein coding transcripts that play an important role in pancreatic carcinogenesis. We herein aimed to meta-analyze the diagnostic and prognostic significance of lncRNA expression profiles in PC. A comprehensive retrieval of eligible studies was performed based on the online databases. Quantitative meta-analyses of the pooled diagnostic parameters and hazard ratios (HRs) were enabled by using standard statistical methods. A total of 16 studies comprising 1386 PC patients were included. The pooled effect sizes exhibited that lncRNA expression profile achieved a combined sensitivity of 0.82 (95% CI: 0.72-0.89), specificity of 0.77 (95% CI: 0.65-0.86) and AUC (area under curve) of 0.87 (95% CI: 0.83-0.89) in distinguishing patients with PC from noncancerous controls. Notably, abnormally expressed lncRNAs were markedly associated with unfavorable overall survival (OS) in PC (univariate analysis: HR = 1.52, 95% CI: 1.04-2.22, P = 0.031; multivariate analysis: HR = 1.55, 95% CI: 1.19-2.02, P = 0.001). Statistical significance was also observed in our stratified analyses grouped by clinicopathologic features. In conclusion, abnormal lncRNA expression profiles could be rated as promising biomarker(s) to enable diagnosis and predict the prognosis of PC.

Expression of Axl and its prognostic significance in human breast cancer.

Breast cancer is the most common malignant cancer and second leading cause of cancer-related death among women, and its prevalence continues to increase. Axl overexpression has been identified in the many types of human cancer, and it has been demonstrated to participate in signaling pathways related to carcinogenesis and cancer development. In the present study, Axl expression was examined by performing immunohistochemical staining in 60 breast cancer tumors and 40 benign breast lesions (25 mammary dysplasia and 15 breast fibroadenoma). In total, 34 (56.67%) cancer tissues and 13 (32.5%) benign breast lesions were classified as exhibiting high levels of Axl expression, indicating a significant association between malignancy and high Axl expression. High Axl expression was also associated with estrogen receptor (ER) positivity (P=0.028), progesterone receptor (PR) positivity (P=0.007), and poor tumor differentiation (P=0.033). No significant associations were observed between Axl expression and age, tumor size, lymph node metastasis, tumor node metastasis staging, human epidermal growth factor receptor 2 and Ki67 antigen. The Kaplan-Meier survival analysis and Cox proportional hazard model both demonstrated that there was no statistical difference between Axl expression and breast cancer prognosis. However, it remains unclear whether the expression of Axl is correlated with the prognosis of luminal type breast cancer patients.

Silencing cyclin-dependent kinase inhibitor 3 inhibits the migration of breast cancer cell lines.

Cyclin-dependent kinase inhibitor 3 (CDKN3) belongs to the dual-specificity protein phosphatase family, which is hypothesized to regulate cell cycle progression in tumor cells. However, whether CDKN3 is a potential therapeutic target for breast cancer remains to be elucidated. The present in vitro study aimed to investigate the potential roles of CDKN3 in breast cancer. Breast cancer cell lines were used to detect CDKN3 expression, and CDKN3 expression was silenced to investigate its role in cell apoptosis, cell cycle arrest and migration. The underlying mechanisms were screened by detecting proliferating cell nuclear antigen (PCNA), Ras homolog gene family, member A (RhoA), vimentin, B­cell lymphoma 2 (Bcl­2) and Bcl­2­associated X protein (Bax) expression. CDKN3 was highly expressed in MCF­7 and BT474 cell lines. The silencing of CDKN3 in MCF­7 and BT474 cell lines promoted cell apoptosis, induced G1 phase cell cycle arrest and inhibited cell migration. The expression levels of PCNA, RhoA, vimentin and Bcl­2 were downregulated following CDKN3 silencing. Conversely, Bax expression was increased, as compared with the vehicle control. These results suggest that CDKN3 acts as an oncogene during breast cancer progression. The in vitro silencing of CDKN3 promoted apoptosis, induced G1 phase cell cycle arrest and inhibited cell migration. Possible mechanisms are associated with the regulation of PCNA, Bcl­2, vimentin, RhoA and Bax expression. CDKN3 may therefore be considered a potential target for the treatment of breast cancer.

Tumor-suppressing roles of miR-214 and miR-218 in breast cancer.

MicroRNAs (miRNAs) are small non-coding RNAs that are key post-transcriptional regulators of gene expression. MicroRNA-214 (miR-214) and microRNA-218 (miR-218) have shown the function of tumor suppressors in various types of human cancers. However, the biological functions of miR-214 and miR-218 in breast cancer have not been elucidated completely. The present study evaluated the expression and biological function of miR-214 and miR-218 in human breast cancer. Our results revealed that the expression of miR-214 and miR-218 were significantly decreased in breast cancer tissues compared with adjacent tissues. The aberrant expression of miR-214 and miR-218 were negatively associated with Ki-67, and the miR-218 expression was positively associated with progesterone receptor (PR) in breast cancer tissues. In vitro, the cell proliferation and migration were decreased, cell apoptosis was induced, and cell cycle was also disturbed in miR-214 or miR-218 overexpressed breast cancer cells. Our results demonstrated that miR-214 and miR-218 function as tumor suppressors in breast cancer, and may become biomarkers and potential therapeutic targets in breast cancer.

Combination of SF1126 and gefitinib induces apoptosis of triple-negative breast cancer cells through the PI3K/AKT-mTOR pathway.

To investigate the apoptotic mechanism of triple-negative breast cancer (TNBC) cells induced by gefitinib and PI3K inhibitor SF1126. MDA-MB-231, MDA-MB-436, and MCF-7 cells were incubated with 0.1 µmol/l gefitinib, 1 µmol/l gefitinib, 10 µmol/l gefitinib, 1 µmol/l SF1126, 0.1 µmol/l gefitinib+1 µmol/l SF1126, 1 µmol/l gefitinib+1 µmol/l SF1126, and 10 µmol/l gefitinib+1 µmol/l SF1126. Then, cell viability and survival were determined using an 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay and Hoechst staining. The apoptosis-related factors and phosphoinositide-3-kinase/protein kinase B, the mammalian target of rapamycin (PI3K/AKT-mTOR) signaling pathway-related factors were detected by western blot. For TNBC cells, cell viability or survival was not significantly inhibited by gefitinib or SF1126 alone; however, marked cell apoptosis was noted in the gefitinib and SF1126 combination groups, and this effect was dose dependent. Also, the expressions of apoptosis markers, such as cleaved caspase-3, Bcl-2/Bax, were altered by the gefitinib and SF1126 combination. Moreover, phosphorylated AKT (p-AKT) and 70 kDa ribosomal protein S6-kinase (p-p70S6K) were also inhibited by the gefitinib and SF1126 combination, which may be responsible for the apoptosis. Gefitinib combined with SF1126 could induce cell apoptosis in TNBC cells and this effect was mediated through the EGFR-PI3K-AKT-mTOR-p70S6K pathway. Our studies have set the stage for future clinical trials of TNBC therapy by the combination of gefitinib and SF1126.

Identification of differently expressed genes with specific SNP Loci for breast cancer by the integration of SNP and gene expression profiling analyses.

This study aims to explore the relationship between gene polymorphism and breast cancer, and to screen DEGs (differentially expressed genes) with SNPs (single nucleotide polymorphisms) related to breast cancer. The SNPs of 17 patients and the preprocessed SNP profiling GSE 32258 (38 cases of normal breast cells) were combined to identify their correlation with breast cancer using chi-square test. The gene expression profiling batch8_9 (38 cases of patients and 8 cases of normal tissue) was preprocessed with limma package, and the DEGs were filtered out. Then fisher's method was applied to integrate DEGs and SNPs associated with breast cancer. With NetBox software, TRED (Transcriptional Regulatory Element Database) and UCSC (University of California Santa Cruz) database, genes-associated network and transcriptional regulatory network were constructed using cytoscape software. Further, GO (Gene Ontology) and KEGG analyses were performed for genes in the networks by using siggenes. In total, 332 DEGs were identified. There were 160 breast cancer-related SNPs related to 106 genes of gene expression profiling (19 were significant DEGs). Finally, 11co-correlated DEGs were selected. In genes-associated network, 9 significant DEGs were correlated to 23 LINKER genes while, in transcriptional regulatory network, E2F1 had regulatory relationships with 7 DEGs including MTUS1, CD44, CCNB1 and CCND2. KRAS with SNP locus of rs1137282 was involved in 35 KEGG pathways. The genes of MTUS1, CD44, CCNB1, CCND2 and KRAS with specific SNP loci may be used as biomarkers for diagnosis of breast cancer. Besides, E2F1 was recognized as the transcription factor of 7 DEGs including MTUS1, CD44, CCNB1 and CCND2.

[Pathogenesis of uropathogenic Escherichia coli: role of outer membrane protein T and the mechanism].

OBJECTIVE: To study the role of outer membrane protein T (OmpT) in the pathogenesis of uropathogenic Escherichia.coli. METHODS: In cultured human bladder epithelial cell line 5637, we examined the adhesion ability of wild-type (CFT073), ompT gene knockout (COTD), and revertant (pST) strains of E.coli to the cells and the extracellular matrix (ECM). The expressions of the adhesion gene iha and virulence gene iroN were detected by real-time PCR. Murine models of urinary tract infection with the 3 strains were established to evaluate the bacterial burden of the bladder and kidney tissue and bacterial counts in blood. We also detected the expressions of interleukin-6 (IL-6) and IL-8 in the bladder and kidney tissues of the mice. RESULT: The COTD strain showed a significantly lower cell adhesion rate than CFT073 strain [(4.62∓0.39)% vs (8.81∓1.13)%, P<0.05] with also a lower ECM-adhesion rate [(4.95∓0.59)% vs (8.85∓0.79)%, P<0.05]. The mRNA expressions of iha and iroN in CFT073 strain were 2.1 and 3.8 times that of COTD strain. In the mouse model, the mean bacterial load of CFT073 strain in the bladder tissue was 6.36∓0.06, significantly greater than that of COTD (6.01∓0.07) and revertant (6.29∓0.06) strains (P<0.05); the bacterial load of CFT073 strain in the kidney tissue was also significantly higher than that of COTD strain (6.25∓0.05 vs 5.87∓0.06, P<0.05). In mice infected with the wild-type, knockout, and revertant strains, the detection rates of IL-6, which were identical to those of IL-8, in the inflammatory bladder and kidney tissues were 60%, 12.5%, and 50%, respectively. CONCLUSIONS: OmpT may regulate the expression of the adhesion gene iha and the transferrin gene iroN to affect the adhesion of uropathogenic E.coli to host cells.

Micellar nanoparticles loaded with gemcitabine and doxorubicin showed synergistic effect.

Gemcitabine and doxorubicin were separately chemically linked to biodegradable polymers to prepare polymer-gemcitabine and polymer-doxorubicin conjugates. Moreover, the two conjugates can self-assemble into micelles with both gemcitabine and doxorubicin. In this way, the two anticancer drugs were combined. The in vitro MTT assay with these combined drugs showed synergistic effect compared to single use of each drug.